We are in process of studying the development and breakdown of aneurogenic (An.) limb muscle in salamander larvae. We are now focusing on isolating the factors which are involved in the muscle breakdown. At present preliminary evidence indicates the following: 1. Muscle breakdown in aneurogenic (An.) limbs seems not to be a function of nutrition. An. limbs grafted orthotopically to normal larvae and maintained nerveless by host nerve section continue to show (by E.M.) muscle breakdown while An.limb grafts allowed to become innervated by host brachial nerves exhibit excellent muscle structure. An. larvae parabiosed to normal larvae for nutritional maintenance still show muscle breakdown. Animals allowed to develop in a starved condition exhibit atrophic changes in muscle but not the drastic changes seen in aneurogenic muscle. 2. Inactivation of normal limbs by post-cranial severance of the spinal cord results in partial limb muscle breakdown but never complete dissociation as is found in aneurogenic limbs. 3. Electrical stimulation leading to twitching of the aneurogenic limb for 1 hr. per day (15 pps, 1ms delay, 175 ms duration) delays the breakdown of the muscle. It will be interesting also to see if aneurogenic muscle in a late stage of breakdown can be reverted back to a less disorganized state by electrical stimulation.. 4. Aneurogenic limbs amputated during early phases of muscle breakdown will regenerate and new muscle differentiates in the regenerate. This muscle then breaks down. In the course of completion of regeneration the muscle of the remaining limb stump, (which gave rise to the regenerate) disappears. Muscle breakdown begins proximally (in the upper arm) and proceeds distally. We are interested in re-regeneration of these limbs to see if muscle continues to redifferentiate. If not at what stage does it stop? Will regeneration continue even if no muscle appears in the regenerate? The stimulator effect of regeneration on prolonging nerveless muscle in the limb is greatly intriguing.